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Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus

Nanotubes can be loaded with doxorubicin to mediate neuroblastoma cell death.High power (100× lens and 4× optical zoom) brightfield ((a) left) and fluorescent ((a) middle) microscopy of doxorubicin loaded nanotubes, visible via the intrinsic fluorescence of doxorubicin (emission at 488 nm: overlay (a) right). Both magnetic and non-magnetic nanotubes show no cytotoxicity towards SHSY5Y neuroblastoma at all concentrations tested (b), but cause over 40% loss in viability when incubated for 24 hours with doxorubicin prior to cell treatment (c) (n = 4, scale bars = 5 μm).
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f6: Nanotubes can be loaded with doxorubicin to mediate neuroblastoma cell death.High power (100× lens and 4× optical zoom) brightfield ((a) left) and fluorescent ((a) middle) microscopy of doxorubicin loaded nanotubes, visible via the intrinsic fluorescence of doxorubicin (emission at 488 nm: overlay (a) right). Both magnetic and non-magnetic nanotubes show no cytotoxicity towards SHSY5Y neuroblastoma at all concentrations tested (b), but cause over 40% loss in viability when incubated for 24 hours with doxorubicin prior to cell treatment (c) (n = 4, scale bars = 5 μm).

Mentions: Dried nanotubes could be filled with a solution of doxorubicin in water by simple re-dispersion in the solution. For cytotoxicity experiments a high concentration of doxorubicin loading solution was chosen (1.5 mg/mL), however, for specific loading and release analysis a much lower concentration of 80 μg/mL was used to allow accurate detection of how much doxorubicin left the loading solution to enter the nanotubes. After loading the nanotubes with the doxorubicin solution, the nanotubes were centrifuged and washed with PBS extensively to remove any free doxorubicin. Fluorescent microscopy imaging (Fig. 6a) showed the doxorubicin loaded nanotubes to have a fluorescent emission at 488 (FITC filter) due to the intrinsic fluorescence of doxorubicin, but one cannot distinguish if the doxorubicin is within the pore or loaded to the tube wall. Doxorubicin uptake by the nanotubes, could be quantified by the change in absorbance of a doxorubicin loading solution at a concentration of 80 μg/ml, before and after the addition of empty nanotubes. An average of 38 ng of doxorubicin was loaded per μg of nanotubes (see Supplementary Table 4), and the release of the drug could be observed over a period of 8 days (maximum time analyzed) (Supplementary Fig. 12). Although it is unclear what drives such efficient loading (see Supplementary Fig. 12 insert to see how dark red the nanotube pellet becomes), others have reasoned that loading to polymers occurs via hydrophobic interaction between the doxorubicin and the polymer29. It is interesting to note that the polymers in that study29 were of similar compositions to the EGDMA nanotubes in terms of ethylene glycol was the main component, and poly(propylene glycol) was used to adjust the hydrophobicity (EGDMA is more hydrophobic than PEG). The sustained release profile observed may suggest that the doxorubicin is up-taken within the pore (not just surface loading) so that the 1D effect of a single or double open tube end (i.e. low pore surface to internal volume ratio - slow release) prolongs the release, as oppose to absorption to the nanotube wall (high surface area to volume ratio – quick release).


Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

Nanotubes can be loaded with doxorubicin to mediate neuroblastoma cell death.High power (100× lens and 4× optical zoom) brightfield ((a) left) and fluorescent ((a) middle) microscopy of doxorubicin loaded nanotubes, visible via the intrinsic fluorescence of doxorubicin (emission at 488 nm: overlay (a) right). Both magnetic and non-magnetic nanotubes show no cytotoxicity towards SHSY5Y neuroblastoma at all concentrations tested (b), but cause over 40% loss in viability when incubated for 24 hours with doxorubicin prior to cell treatment (c) (n = 4, scale bars = 5 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664922&req=5

f6: Nanotubes can be loaded with doxorubicin to mediate neuroblastoma cell death.High power (100× lens and 4× optical zoom) brightfield ((a) left) and fluorescent ((a) middle) microscopy of doxorubicin loaded nanotubes, visible via the intrinsic fluorescence of doxorubicin (emission at 488 nm: overlay (a) right). Both magnetic and non-magnetic nanotubes show no cytotoxicity towards SHSY5Y neuroblastoma at all concentrations tested (b), but cause over 40% loss in viability when incubated for 24 hours with doxorubicin prior to cell treatment (c) (n = 4, scale bars = 5 μm).
Mentions: Dried nanotubes could be filled with a solution of doxorubicin in water by simple re-dispersion in the solution. For cytotoxicity experiments a high concentration of doxorubicin loading solution was chosen (1.5 mg/mL), however, for specific loading and release analysis a much lower concentration of 80 μg/mL was used to allow accurate detection of how much doxorubicin left the loading solution to enter the nanotubes. After loading the nanotubes with the doxorubicin solution, the nanotubes were centrifuged and washed with PBS extensively to remove any free doxorubicin. Fluorescent microscopy imaging (Fig. 6a) showed the doxorubicin loaded nanotubes to have a fluorescent emission at 488 (FITC filter) due to the intrinsic fluorescence of doxorubicin, but one cannot distinguish if the doxorubicin is within the pore or loaded to the tube wall. Doxorubicin uptake by the nanotubes, could be quantified by the change in absorbance of a doxorubicin loading solution at a concentration of 80 μg/ml, before and after the addition of empty nanotubes. An average of 38 ng of doxorubicin was loaded per μg of nanotubes (see Supplementary Table 4), and the release of the drug could be observed over a period of 8 days (maximum time analyzed) (Supplementary Fig. 12). Although it is unclear what drives such efficient loading (see Supplementary Fig. 12 insert to see how dark red the nanotube pellet becomes), others have reasoned that loading to polymers occurs via hydrophobic interaction between the doxorubicin and the polymer29. It is interesting to note that the polymers in that study29 were of similar compositions to the EGDMA nanotubes in terms of ethylene glycol was the main component, and poly(propylene glycol) was used to adjust the hydrophobicity (EGDMA is more hydrophobic than PEG). The sustained release profile observed may suggest that the doxorubicin is up-taken within the pore (not just surface loading) so that the 1D effect of a single or double open tube end (i.e. low pore surface to internal volume ratio - slow release) prolongs the release, as oppose to absorption to the nanotube wall (high surface area to volume ratio – quick release).

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus